Publications by authors named "Willem A Nolen"

228 Publications

Are personality disorders in bipolar patients more frequent in the US than Europe?

Eur Neuropsychopharmacol 2022 05 25;58:47-54. Epub 2022 Feb 25.

Biostatistician Bipolar Collaborative Network, Chevy Chase, MD, United States.

Objective: Bipolar patients in the United States (US) compared to those from the Netherlands and Germany (here abbrev. as "Europe") have more Axis I comorbidities and more poor prognosis factors such as early onset and psychosocial adversity in childhood. We wished to examine whether these differences also extended to Axis II personality disorders (PDs).

Methods: 793 outpatients with bipolar disorder diagnosed by SCID gave informed consent for participating in a prospective longitudinal follow up study with clinician ratings at each visit. They completed detailed patient questionnaires and a 99 item personality disorder inventory (PDQ-4). US versus European differences in PDs were examined in univariate analyses and then logistic regressions, controlling for severity of depression, age, gender, and other poor prognosis factors.

Results: In the univariate analysis, 7 PDs were more prevalent in the US than in Europe, including antisocial, avoidant, borderline, depressive, histrionic, obsessive compulsive, and schizoid PDs. In the multivariate analysis, the last 4 of these PDs remained independently greater in the US than Europe.

Conclusions: Although limited by use of self report and other potentially confounding factors, multiple PDs were more prevalent in the US than in Europe, but these preliminary findings need to be confirmed using other methodologies. Other poor prognosis factors are prevalent in the US, including early age of onset, more childhood adversity, anxiety and substance abuse comorbidity, and more episodes and rapid cycling. The interactions among these variables in relationship to the more adverse course of illness in the US than in Europe require further study.
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http://dx.doi.org/10.1016/j.euroneuro.2022.02.007DOI Listing
May 2022

Pharmacological treatment for psychotic depression.

Cochrane Database Syst Rev 2021 12 7;12:CD004044. Epub 2021 Dec 7.

Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Background: Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: monotherapy with an antidepressant, monotherapy with an antipsychotic, another treatment (e.g. mifepristone), or combination of an antidepressant plus an antipsychotic. This is an update of a review first published in 2005 and last updated in 2015.

Objectives: 1. To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, mifepristone monotherapy, and the combination of an antidepressant plus an antipsychotic versus placebo and/or each other. 2. To assess whether differences in response to treatment in the current episode are related to non-response to prior treatment.

Search Methods: A search of the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR); Ovid MEDLINE (1950-); Embase (1974-); and PsycINFO (1960-) was conducted on 21 February 2020. Reference lists of all included studies and related reviews were screened and key study authors contacted.

Selection Criteria: All randomised controlled trials (RCTs) that included participants with acute major depression with psychotic features, as well as RCTs consisting of participants with acute major depression with or without psychotic features, that reported separately on the subgroup of participants with psychotic features.

Data Collection And Analysis: Two review authors independently extracted data and assessed risk of bias in the included studies, according to criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Data were entered into RevMan 5.1. We used intention-to-treat data. Primary outcomes were clinical response for efficacy and overall dropout rate for harm/tolerance. Secondary outcome were remission of depression, change from baseline severity score, quality of life, and dropout rate due to adverse effects. For dichotomous efficacy outcomes (i.e. response and overall dropout), risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.  Regarding the primary outcome of harm, only overall dropout rates were available for all studies. If the study did not report any of the response criteria as defined above, remission as defined here could be used as an alternative. For continuously distributed outcomes, it was not possible to extract data from the RCTs.  MAIN RESULTS: The search identified 3947 abstracts, but only 12 RCTs with a total of 929 participants could be included in the review. Because of clinical heterogeneity, few meta-analyses were possible. The main outcome was reduction in severity (response) of depression, not of psychosis. For depression response, we found no evidence of a difference between antidepressant and placebo (RR 8.40, 95% CI 0.50 to 142.27; participants = 27, studies = 1; very low-certainty evidence) or between antipsychotic and placebo (RR 1.13, 95% CI 0.74 to 1.73; participants = 201, studies = 2; very low-certainty evidence). Furthermore, we found no evidence of a difference in overall dropouts with antidepressant (RR 1.24, 95% CI 0.34 to 4.51; participants = 27, studies = 1; very low-certainty evidence) or antipsychotic monotherapy (RR 0.79, 95% CI 0.57 to 1.08; participants = 201, studies = 2; very low-certainty evidence). No evidence suggests a difference in depression response (RR 2.09, 95% CI 0.64 to 6.82; participants = 36, studies = 1; very low-certainty evidence) or overall dropouts (RR 1.79, 95% CI 0.18 to 18.02; participants = 36, studies = 1; very low-certainty evidence) between antidepressant and antipsychotic. For depression response, low- to very low-certainty evidence suggests that the combination of an antidepressant plus an antipsychotic may be more effective than antipsychotic monotherapy (RR 1.83, 95% CI 1.40 to 2.38; participants = 447, studies = 4), more effective than antidepressant monotherapy (RR 1.42, 95% CI 1.11 to 1.80; participants = 245, studies = 5), and more effective than placebo (RR 1.86, 95% CI 1.23 to 2.82; participants = 148, studies = 2). Very low-certainty evidence suggests no difference in overall dropouts between the combination of an antidepressant plus an antipsychotic versus antipsychotic monotherapy (RR 0.79, 95% CI 0.63 to 1.01; participants = 447, studies = 4), antidepressant monotherapy (RR 0.91, 95% CI 0.55 to 1.50; participants = 245, studies = 5), or placebo alone (RR 0.75, 95% CI 0.48 to 1.18; participants = 148, studies = 2). No study measured change in depression severity from baseline, quality of life, or dropouts due to adverse events. We found no RCTs with mifepristone that fulfilled our inclusion criteria. Risk of bias is considerable: we noted differences between studies with regards to diagnosis, uncertainties around randomisation and allocation concealment, treatment interventions (pharmacological differences between various antidepressants and antipsychotics), and outcome criteria.

Authors' Conclusions: Psychotic depression is heavily under-studied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone. Evidence for efficacy of mifepristone is lacking.
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http://dx.doi.org/10.1002/14651858.CD004044.pub5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651069PMC
December 2021

Mania and bipolar depression: complementing not opposing poles-a post-hoc analysis of mixed features in manic and hypomanic episodes.

Int J Bipolar Disord 2021 Nov 16;9(1):36. Epub 2021 Nov 16.

Department of Psychiatry and Psychotherapy Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Background: Depending on the classification system used, 5-40% of manic subjects present with concomitant depressive symptoms. This post-hoc analysis evaluates the hypothesis that (hypo)manic subjects have a higher burden of depression than non-(hypo)manic subjects.

Methods: Data from 806 Bipolar I or II participants of the Stanley Foundation Bipolar Network (SFBN) were analyzed, comprising 17,937 visits. A split data approach was used to separate evaluation and verification in independent samples. For verification of our hypotheses, we compared mean IDS-C scores ratings of non-manic, hypomanic and manic patients. Data were stored on an SQL-server and extracted using standard SQL functions. Linear correlation coefficients and pivotal tables were used to characterize patient groups.

Results: Mean age of participants was 40 ± 12 years (range 18-81). 460 patients (57.1%) were female and 624 were diagnosed as having bipolar I disorder (77.4%) and 182 with bipolar II (22.6%). Data of 17,937 visits were available for analyses, split into odd and even patient numbers and stratified into three groups by YMRS-scores: not manic < 12, hypomanic < 21, manic < 30. Average IDS-C sum scores in manic or hypomanic states were significantly higher (p < .001) than for non-manic states. (Hypo)manic female patients were likely to show more depressive symptoms than males (p < .001). Similar results were obtained when only the core items of the YMRS or only the number of depressive symptoms were considered. Analyzing the frequency of (hypo)manic mixed states applying a proxy of the DSM-5 mixed features specifier extracted from the IDS-C, we found that almost 50% of the (hypo)manic group visits fulfilled DSM-5 mixed features specifier criteria.

Conclusion: Subjects with a higher manic symptom load are also significantly more likely to experience a higher number of depressive symptoms. Mania and depression are not opposing poles of bipolarity but complement each other.
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http://dx.doi.org/10.1186/s40345-021-00241-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593087PMC
November 2021

The course of bipolar disorder in pregnant versus non-pregnant women.

Int J Bipolar Disord 2021 Nov 4;9(1):35. Epub 2021 Nov 4.

Amsterdam UMC, Vrije Universiteit, Psychiatry, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.

Background And Rationale: Although it has been suggested that pregnancy may influence the course of bipolar disorder (BD), studies show contradictory results. Until now, no studies included a finegrained validated method to report mood symptoms on a daily basis, such as the lifechart method (LCM). The aim of the present study is to investigate the course of BD during pregnancy by comparing LCM scores of pregnant and non-pregnant women.

Methods: Study design: Comparison of LCM scores of two prospective observational BD cohort studies, a cohort of pregnant women (n = 34) and a cohort of non-pregnant women of childbearing age (n = 52). Main study parameters are: (1) proportions of symptomatic and non-symptomatic days; (2) symptom severity, frequency, and duration of episodes; (3) state sequences, longitudinal variation of symptom severity scores.

Results: No differences in clinical course variables (symptomatic days, average severity scores, frequency, and duration of episodes in BD were found between pregnant and non-pregnant women. With a combination of State Sequence Analysis (SSA) and cluster analysis on the sequences of daily mood scores three comparable clusters were found in both samples: euthymic, moderately ill and severely ill. The distribution differences between pregnant and non-pregnant women were significant, with a majority of the pregnant women (68%) belonging to the moderately ill cluster and a majority of the non-pregnant women (46%) to the euthymic cluster. In pregnant women the average daily variation in mood symptoms as assessed with Shannon's entropy was less than in non-pregnant women (respectively 0.43 versus 0.56).

Conclusions: Although the use of daily mood scores revealed no difference in overall course of BD in pregnant versus non-pregnant women, more pregnant than non-pregnant women belonged to the moderately ill cluster, and during pregnancy the variation in mood state was less than in non-pregnant women. Further research is necessary to clarify these findings.
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http://dx.doi.org/10.1186/s40345-021-00239-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566649PMC
November 2021

Association of the neutrophil to lymphocyte ratio and white blood cell count with response to pharmacotherapy in unipolar psychotic depression: An exploratory analysis.

Brain Behav Immun Health 2021 10 5;16:100319. Epub 2021 Aug 5.

Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands.

Background: Low-grade inflammation occurs in a subgroup of patients with Major Depressive Disorder (MDD) and may be associated with response to antidepressant medications. The Neutrophil to Lymphocyte Ratio (NLR) and total White Blood cell Count (WBC) are markers of systemic inflammation which have not been investigated as predictors for outcome to pharmacotherapy in unipolar depression yet. Moreover, the association between inflammation and treatment response has not been studied in unipolar Psychotic Depression (PD). We conducted an exploratory analysis to examine the prognostic significance of NLR and WBC in pharmacotherapy of PD.

Methods: Baseline NLR and WBC were examined in their association with response to seven weeks of treatment with antidepressants (venlafaxine or imipramine) and the combination of an antidepressant with an antipsychotic (venlafaxine plus quetiapine) in 87 patients with PD. Logistic regression models were adjusted for age, gender, Body Mass Index (BMI), depression severity, duration of the current episode and number of previous depressive episodes. Secondary outcomes were remission of depression and disappearance of psychotic symptoms.

Results: Higher NLR was associated with increased response to pharmacotherapy (Exp(B) 1.66, 95 % CI 1.03-2.66, = 0.036), but not with remission of depression or disappearance of psychotic symptoms. WBC was not associated with any of the outcome measures.

Conclusion: NLR may be a novel, inexpensive and widely available biomarker associated with response to pharmacotherapy in PD. The association between white blood cell measures and treatment outcome should be further investigated for different types of antidepressants in PD and in non-psychotic MDD.
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http://dx.doi.org/10.1016/j.bbih.2021.100319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611545PMC
October 2021

Plasma androgens and the presence and course of depression in a large cohort of men.

Psychoneuroendocrinology 2021 08 19;130:105278. Epub 2021 May 19.

Department of Psychiatry, University of Groningen / University Medical Center Groningen, 9700 RB, PO Box 30.001 (CC 43), Groningen, The Netherlands. Electronic address:

Background: Hypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or additionally to core emotional symptoms such as sadness and anhedonia. We examined whether androgen levels 1) differ between men with and without MDD cross-sectionally, 2) are associated with an elevated risk for onset of MDD prospectively, and 3) associate with all individual MDD symptoms, or only with hypogonadism overlapping symptoms.

Methods: In 823 men (mean age 43.5 years), baseline plasma levels of total testosterone, 5α-dihydrotestosterone (5α-DHT), and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulphate (DHEAS) and sex hormone binding globulin with radioimmunoassay, whereas free testosterone was calculated. MDD status was assessed at baseline and after two years using structured interviews and individual MDD symptoms were self-rated at baseline, and after one and two years.

Results: None of the androgen levels were associated with current or onset (incidence or recurrence) of MDD. Free testosterone was only inversely associated with interest in sex. Also, androstenedione and DHEAS were positively associated with some individual MDD symptoms, and 5α-DHT levels showed non-linear associations (both with low and high levels) with MDD symptom severity and several individual MDD symptoms.

Conclusions: These results support the idea that circulating androgens synthesised by the testes are of limited clinical relevance to MDD in adult men, but levels of androstenedione, DHEAS and 5α-DHT may be associated with some individual MDD symptoms.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105278DOI Listing
August 2021

25 Years of the International Bipolar Collaborative Network (BCN).

Int J Bipolar Disord 2021 Apr 2;9(1):13. Epub 2021 Apr 2.

Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: The Stanley Foundation Bipolar Treatment Outcome Network (SFBN) recruited more than 900 outpatients from 1995 to 2002 from 4 sites in the United States (US) and 3 in the Netherlands and Germany (abbreviated as Europe). When funding was discontinued, the international group of investigators continued to work together as the Bipolar Collaborative Network (BCN), publishing so far 87 peer-reviewed manuscripts. On the 25th year anniversary of its founding, publication of a brief summary of some of the major findings appeared appropriate. Important insights into the course and treatment of adult outpatients with bipolar disorder were revealed and some methodological issues and lessons learned will be discussed.

Results: The illness is recurrent and pernicious and difficult to bring to a long-term remission. Virtually all aspects of the illness were more prevalent in the US compared to Europe. This included vastly more patients with early onset illness and those with more psychosocial adversity in childhood; more genetic vulnerability; more anxiety and substance abuse comorbidity; more episodes and rapid cycling; and more treatment non-responsiveness.

Conclusions: The findings provide a road map for a new round of much needed clinical treatment research studies. They also emphasize the need for the formation of a new network focusing on child and youth onset of mood disorders with a goal to achieve early precision diagnostics for intervention and prevention in attempting to make the course of bipolar illness more benign.
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http://dx.doi.org/10.1186/s40345-020-00218-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019011PMC
April 2021

Guideline concordance and outcome in long-term naturalistic treatment of bipolar disorder - a one-year longitudinal study using latent change models.

J Affect Disord 2021 03 29;283:395-401. Epub 2020 Dec 29.

Altrecht Institute for Mental Health Care, Lange Nieuwstraat 119, 3512 PG, Utrecht, the Netherlands; Amsterdam University Medical Center / Vrije Universiteit, Department of Psychiatry & Amsterdam Public Health research institute, Oldenaller 1, 1081 HJ, Amsterdam, the Netherlands. Electronic address:

Background: Only few studies investigated the relation between concordance with treatment guidelines and treatment outcome in everyday treatment of bipolar disorder (BD). Prospective studies are scarce.

Methods: A nationwide, naturalistic, prospective study on the relation between guideline concordance and treatment outcome in the long-term outpatient treatment of patients with BD. Participants completed a survey on treatments received and various outcome measures at baseline and after one year.

Results: Of 839 patients who completed the baseline survey, 615 (73.3%) also completed the follow-up survey. Consistent with our a priori hypothesis, cross-sectional analyses at baseline showed correlations between guideline concordance with quality of life (r = .17, p < .001), treatment satisfaction (r = .17, p <.001), and impaired functioning (r = -.10, p = .04). At follow-up, guideline concordance was correlated with severity of illness (r = -.10, p = .05), quality of life (r = .18, p < .001), and treatment satisfaction (r = .15, p < .001). Concerning three additional hypotheses on longitudinal relations between concordance and outcome measures, only a positive relation was found between change in guideline concordance and change in quality of life.

Limitations: Selection bias may have occurred by inclusion of patients with neither a very severe nor a very mild course of illness.

Conclusions: Although guideline concordance was high throughout the study, change in guideline concordance was positively associated with change in quality of life, suggesting that especially in long-term treatment, continuous efforts to optimize ongoing treatment is essential.
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http://dx.doi.org/10.1016/j.jad.2020.12.106DOI Listing
March 2021

Plasma androgens and the presence and course of depression in a large cohort of women.

Transl Psychiatry 2021 02 12;11(1):124. Epub 2021 Feb 12.

University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.

Major depressive disorder (MDD) has a higher prevalence in women with supraphysiologic androgen levels. Whether there is also an association between depression and androgen levels in the physiological range, is unknown. This study examined if women with current MDD have higher androgen levels compared to women who have never had MDD, and if androgen levels are associated with onset and remission of MDD. In 1659 women (513 current MDD, 754 remitted MDD, and 392 never MDD), baseline plasma levels of total testosterone, 5α-dihydrotestosterone, and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulfate and sex hormone binding globulin (SHBG) with radioimmunoassays. Free testosterone was calculated. MDD status was assessed at baseline, and at 2 and 4 years follow-up. Women were aged between 18 and 65 years (mean age 41) with total testosterone levels in the physiological range (geometric mean 0.72 nmol/L [95% CI 0.27-1.93]). After adjusting for covariates and multiple testing, women with current MDD had a higher mean free testosterone than women who never had MDD (adjusted geometric mean 8.50 vs. 7.55 pmol/L, p = 0.0005), but this difference was not large enough to be considered clinically meaningful as it was consistent with statistical equivalence. Levels of other androgens and SHBG did not differ and were also statistically equivalent between the groups. None of the androgens or SHBG levels predicted onset or remission of MDD. Our findings support the idea that plasma androgens within the physiological range have no or only limited effects on depressive disorders in women.
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http://dx.doi.org/10.1038/s41398-021-01249-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881099PMC
February 2021

Development and implementation of guidelines for the management of depression: a systematic review.

Bull World Health Organ 2020 Oct 27;98(10):683-697H. Epub 2020 Aug 27.

School of Clinical Medicine, The University of Queensland, Brisbane, Australia.

Objective: To evaluate the development and implementation of clinical practice guidelines for the management of depression globally.

Methods: We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries.

Findings: We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence.

Conclusion: Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes.
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http://dx.doi.org/10.2471/BLT.20.251405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652558PMC
October 2020

Development and implementation of guidelines for the management of depression: a systematic review.

Bull World Health Organ 2020 Oct 27;98(10):683-697H. Epub 2020 Aug 27.

School of Clinical Medicine, The University of Queensland, Brisbane, Australia.

Objective: To evaluate the development and implementation of clinical practice guidelines for the management of depression globally.

Methods: We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries.

Findings: We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence.

Conclusion: Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes.
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http://dx.doi.org/10.2471/BLT.20.251405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652558PMC
October 2020

Lithium: The best current treatment for the well-informed bipolar patient.

Bipolar Disord 2021 02 26;23(1):92. Epub 2020 Oct 26.

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.

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http://dx.doi.org/10.1111/bdi.13007DOI Listing
February 2021

Psychomotor Retardation and the prognosis of antidepressant treatment in patients with unipolar Psychotic Depression.

J Psychiatr Res 2020 11 9;130:321-326. Epub 2020 Aug 9.

Department of Psychiatry, Department of Psychiatry, Radboudumc, Nijmegen, the Netherlands.

Background: Psychomotor Retardation is a key symptom of Major Depressive Disorder. According to the literature its presence may affect the prognosis of treatment. Aim of the present study is to investigate the prognostic role of Psychomotor Retardation in patients with unipolar Psychotic Depression who are under antidepressant treatment.

Methods: The Salpetriere Retardation Rating Scale was administered at baseline and after 6 weeks to 122 patients with unipolar Psychotic Depression who were randomly allocated to treatment with imipramine, venlafaxine or venlafaxine plus quetiapine. We studied the effects of Psychomotor Retardation on both depression and psychosis related outcome measures.

Results: 73% of the patients had Psychomotor Retardation at baseline against 35% after six weeks of treatment. The presence of Psychomotor Retardation predicted lower depression remission rates in addition to a higher persistence of delusions. After six weeks of treatment, venlafaxine was associated with higher levels of Psychomotor Retardation compared to imipramine and venlafaxine plus quetiapine.

Conclusions: Our data confirm that Psychomotor Retardation is a severity marker of unipolar Psychotic Depression. It is highly prevalent and predicts lower effectivity of antidepressant psychopharmacological treatment.
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http://dx.doi.org/10.1016/j.jpsychires.2020.07.020DOI Listing
November 2020

Double jeopardy in the United States: Early onset bipolar disorder and treatment delay.

Psychiatry Res 2020 10 3;292:113274. Epub 2020 Jul 3.

University Medical Center, University of Groningen, Groningen, the Netherlands.

Background: Evidence is emerging that early onset bipolar disorder and the duration of the delay to first treatment are both risk factors for poor treatment outcome. We report on the incidence and implications of these two risk factors in patients from the United States (US) versus Europe.

Methods: Age of onset and age at first treatment for depression or mania was assessed in 967 outpatients with bipolar disorder who gave informed consent for participation and filling out a detailed questionnaire. Age at onset and treatment delay were compared in the 675 patients from the US and 292 from the Netherlands and Germany (abbreviated as Europe). Both were then graphed and analyzed.

Results: Age of onset of bipolar disorder was earlier in the US than in Europeans by an average of 6-7 years with similar results in those with first onsets of depression or of mania. Delay to first treatment was strongly inversely related to age of onset and was twice as long in the US than in Europe, and especially different for mania in adolescents. The longer delay to treatment in the US was not solely due to earlier age of onset.

Conclusions: Treatment delay is a remedial risk factor and could be shortened with better recognition of the higher incidence of early onset bipolar disorder in the US, which also associated with more genetic and environmental vulnerability factors compared to Europe. New treatment and research initiatives are needed to address these liabilities so that children with bipolar achieve more positive long-term outcomes.
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http://dx.doi.org/10.1016/j.psychres.2020.113274DOI Listing
October 2020

A skewed perspective - A reply to Kovvuru et al.

Bipolar Disord 2021 02 25;23(1):86-87. Epub 2020 Jul 25.

Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark.

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http://dx.doi.org/10.1111/bdi.12977DOI Listing
February 2021

Adding Increased Energy or Activity to Criterion (A) of the DSM-5 Definition of Hypomania and Mania: Effect on the Diagnoses of 907 Patients From the Bipolar Collaborative Network.

J Clin Psychiatry 2019 10 29;80(6). Epub 2019 Oct 29.

Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, VA Palo Alto Health Care System, 3801 Miranda Ave (151 T), Palo Alto, CA 94304.

Objective: According to DSM-IV, criterion (A) for diagnosing a hypomanic/manic episode is mood change (ie, elevated, expansive, or irritable mood). Criterion (A) was redefined in DSM-5, adding increased energy or activity in addition to mood change. We sought to investigate the effect of adding increased energy or activity to criterion (A) for the diagnosis of hypomania/mania and, thus, bipolar disorder.

Methods: This analysis of prospectively collected data from the Bipolar Collaborative Network (1995-2002) includes 907 DSM-IV-TR-diagnosed bipolar outpatients (14,306 visits). The Young Mania Rating Scale (YMRS) was administered monthly and used to define DSM-IV and DSM-5 criterion (A) fulfillment during a hypomanic/manic visit.

Results: Patients were adults (median age = 40; IQR, 33-49), and over half (56%) were women. Median number of contributed visits was 10 (IQR, 4-23). Applying DSM-5 criterion (A) reduced the number of patients experiencing a hypomanic/manic visit by 34%, compared to DSM-IV. Visits fulfilling DSM-5 criterion (A) had higher odds of experiencing elevated levels of all other mania symptoms, compared to fulfilling DSM-IV criterion (A) only. Association between individual symptoms was strongest with mood elevation and energy or activity (OR [95% CL] = 8.65, [7.91, 9.47]).

Conclusions: The 34% reduction in the number of patients being diagnosed with a hypomanic/manic visit shows that the impact of applying DSM-5 criterion (A) is substantial. Fewer hypomanic/manic episodes may be diagnosed by the stricter DSM-5 criterion (A), but the episodes diagnosed are likely to be more severe. The DSM-5 criteria may in general prevent overdiagnosis of bipolar disorder but possibly at the cost of underdiagnosing hypomanic/manic episodes.
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http://dx.doi.org/10.4088/JCP.19m12834DOI Listing
October 2019

What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium.

Bipolar Disord 2019 08 20;21(5):394-409. Epub 2019 Jun 20.

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.

Aims: To systematically review the existing trials on optimal serum levels for lithium for maintenance treatment of bipolar disorder and to develop clinical recommendations.

Methods: Systematic literature search. Discussion of major characteristics, limitations, methodological quality, and results of selected trials. Delphi survey consisting of clinical questions and corresponding statements. For statements endorsed by at least 80% of the members, consensus was considered as having been achieved.

Results: With strict inclusion criteria no studies could be selected, making it difficult to formulate evidence-based recommendations. After loosening the inclusion criteria 7 trials were selected addressing our aims at least to some extent. Four of these studies suggest better efficacy being associated with lithium serum levels in a range above a lower threshold around 0.45/0.60 and up to 0.80/1.00 mmol/L. These findings support the outcome of the Delphi survey.

Conclusions: For adults with bipolar disorder there was consensus that the standard lithium serum level should be 0.60-0.80 mmol/L with the option to reduce it to 0.40-0.60 mmol/L in case of good response but poor tolerance or to increase it to 0.80-1.00 mmol/L in case of insufficient response and good tolerance. For children and adolescents there was no consensus, but the majority of the members endorsed the same recommendation. For the elderly there was also no consensus, but the majority of the members endorsed a more conservative approach: usually 0.40-0.60 mmol/L, with the option to go to maximally 0.70 or 0.80 mmol/L at ages 65-79 years, and to maximally 0.70 mmol/L over age 80 years.
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http://dx.doi.org/10.1111/bdi.12805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688930PMC
August 2019

Cost-effectiveness, cost-utility and the budget impact of antidepressants versus preventive cognitive therapy with or without tapering of antidepressants.

BJPsych Open 2019 Jan;5(1):e12

Professor of Clinical Psychology in Psychiatry,Amsterdam UMC, location AMC,Department of Psychiatry,University of Amsterdam,the Netherlands.

Background: As depression has a recurrent course, relapse and recurrence prevention is essential.AimsIn our randomised controlled trial (registered with the Nederlands trial register, identifier: NTR1907), we found that adding preventive cognitive therapy (PCT) to maintenance antidepressants (PCT+AD) yielded substantial protective effects versus antidepressants only in individuals with recurrent depression. Antidepressants were not superior to PCT while tapering antidepressants (PCT/-AD). To inform decision-makers on treatment allocation, we present the corresponding cost-effectiveness, cost-utility and budget impact.

Method: Data were analysed (n = 289) using a societal perspective with 24-months of follow-up, with depression-free days and quality-adjusted life years (QALYs) as health outcomes. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were derived to provide information about cost-effectiveness. The budget impact was examined with a health economic simulation model.

Results: Mean total costs over 24 months were €6814, €10 264 and €13 282 for AD+PCT, antidepressants only and PCT/-AD, respectively. Compared with antidepressants only, PCT+AD resulted in significant improvements in depression-free days but not QALYs. Health gains did not significantly favour antidepressants only versus PCT/-AD. High probabilities were found that PCT+AD versus antidepressants only and antidepressants only versus PCT/-AD were dominant with low willingness-to-pay thresholds. The budget impact analysis showed decreased societal costs for PCT+AD versus antidepressants only and for antidepressants only versus PCT/-AD.

Conclusions: Adding PCT to antidepressants is cost-effective over 24 months and PCT with guided tapering of antidepressants in long-term users might result in extra costs. Future studies examining costs and effects of antidepressants versus psychological interventions over a longer period may identify a break-even point where PCT/-AD will become cost-effective.Declaration of interestC.L.H.B. is co-editor of PLOS One and receives no honorarium for this role. She is also co-developer of the Dutch multidisciplinary clinical guideline for anxiety and depression, for which she receives no remuneration. She is a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this study. C.L.H.B. has presented keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops, some including a fee. She receives royalties from her books and co-edited books and she developed preventive cognitive therapy on the basis of the cognitive model of A. T. Beck. W.A.N. has received grants from the Netherlands Organisation for Health Research and Development and the European Union and honoraria and speakers' fees from Lundbeck and Aristo Pharma, and has served as a consultant for Daleco Pharma.
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http://dx.doi.org/10.1192/bjo.2018.81DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381417PMC
January 2019

Aspirin for recurrence prevention in bipolar disorder-Promising, yet clinically understudied?

Bipolar Disord 2019 02 19;21(1):13-15. Epub 2018 Dec 19.

Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

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http://dx.doi.org/10.1111/bdi.12731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519143PMC
February 2019

Testing a clinical staging model for bipolar disorder using longitudinal life chart data.

Bipolar Disord 2019 05 12;21(3):228-234. Epub 2018 Dec 12.

Department of Psychiatry, Amsterdam Public Health, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Objective: Bipolar disorder has a wide range of clinical manifestations which may progress over time. The aim of this study was to test the applicability of a clinical staging model for bipolar disorder and to gain insight into the nature of the variables influencing progression through consecutive stages.

Methods: Using retrospectively reported longitudinal life chart data of 99 subjects from the Stanley Foundation Bipolar Network Naturalistic Follow-up Study, the occurrence, duration and timely sequence of stages 2-4 were determined per month. A multi-state model was used to calculate progression rates and identify determinants of illness progression. Stages 0, 1 and several other variables were added to the multi-state model to determine their influence on the progression rates.

Results: Five years after onset of BD (stage 2), 72% reached stage 3 (recurrent episodes) and 21% had reached stage 4 (continuous episodes), of whom 8% recovered back to stage 3. The progression from stage 2 to 3 was increased by a biphasic onset for both the depression-mania and the mania-depression course and by male sex.

Conclusions: Staging is a useful model to determine illness progression in longitudinal life chart data. Variables influencing transition rates were successfully identified.
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http://dx.doi.org/10.1111/bdi.12727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590317PMC
May 2019

A nationwide study on concordance with multimodal treatment guidelines in bipolar disorder.

Int J Bipolar Disord 2018 Oct 20;6(1):22. Epub 2018 Oct 20.

Altrecht Institute for Mental Health Care, Utrecht, Nieuwe Houtenseweg 12, 3524 SH, Utrecht, The Netherlands.

Background: Most previous studies on concordance with treatment guidelines for bipolar disorder focused on pharmacotherapy. Few studies have included other treatment modalities.

Aims: To study concordance with the Dutch guideline of various treatment modalities in outpatient treatment settings for patients with bipolar disorder and to identity factors associated with concordance.

Methods: A nationwide non-interventional study using psychiatrists' and patients' surveys.

Results: 839 patients with bipolar or schizoaffective disorder bipolar type were included. Concordance with the guideline was highest for participation of a psychiatrist in the treatment (98%) and for maintenance pharmacotherapy (96%), but lower for supportive treatment (73.5%), use of an emergency plan (70.6%), psychotherapy (52.2%), group psychoeducation (47.2%), and mood monitoring (47%). Presence of a written treatment plan, a more specialized treatment setting, more years of education, and diagnosis of bipolar I disorder versus bipolar II, bipolar NOS, or schizoaffective disorder were significantly associated with better concordance.

Conclusion: In contrast to pharmacotherapy, psychosocial treatments are only implemented to a limited extend in everyday clinical practice in bipolar disorder. More effort is needed to implement non-pharmacological guideline recommendations for bipolar disorder.
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http://dx.doi.org/10.1186/s40345-018-0130-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195496PMC
October 2018

A nationwide study on concordance with multimodal treatment guidelines in bipolar disorder.

Int J Bipolar Disord 2018 Oct 20;6(1):22. Epub 2018 Oct 20.

Altrecht Institute for Mental Health Care, Utrecht, Nieuwe Houtenseweg 12, 3524 SH, Utrecht, The Netherlands.

Background: Most previous studies on concordance with treatment guidelines for bipolar disorder focused on pharmacotherapy. Few studies have included other treatment modalities.

Aims: To study concordance with the Dutch guideline of various treatment modalities in outpatient treatment settings for patients with bipolar disorder and to identity factors associated with concordance.

Methods: A nationwide non-interventional study using psychiatrists' and patients' surveys.

Results: 839 patients with bipolar or schizoaffective disorder bipolar type were included. Concordance with the guideline was highest for participation of a psychiatrist in the treatment (98%) and for maintenance pharmacotherapy (96%), but lower for supportive treatment (73.5%), use of an emergency plan (70.6%), psychotherapy (52.2%), group psychoeducation (47.2%), and mood monitoring (47%). Presence of a written treatment plan, a more specialized treatment setting, more years of education, and diagnosis of bipolar I disorder versus bipolar II, bipolar NOS, or schizoaffective disorder were significantly associated with better concordance.

Conclusion: In contrast to pharmacotherapy, psychosocial treatments are only implemented to a limited extend in everyday clinical practice in bipolar disorder. More effort is needed to implement non-pharmacological guideline recommendations for bipolar disorder.
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http://dx.doi.org/10.1186/s40345-018-0130-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195496PMC
October 2018

A nationwide study on concordance with multimodal treatment guidelines in bipolar disorder.

Int J Bipolar Disord 2018 Oct 20;6(1):22. Epub 2018 Oct 20.

Altrecht Institute for Mental Health Care, Utrecht, Nieuwe Houtenseweg 12, 3524 SH, Utrecht, The Netherlands.

Background: Most previous studies on concordance with treatment guidelines for bipolar disorder focused on pharmacotherapy. Few studies have included other treatment modalities.

Aims: To study concordance with the Dutch guideline of various treatment modalities in outpatient treatment settings for patients with bipolar disorder and to identity factors associated with concordance.

Methods: A nationwide non-interventional study using psychiatrists' and patients' surveys.

Results: 839 patients with bipolar or schizoaffective disorder bipolar type were included. Concordance with the guideline was highest for participation of a psychiatrist in the treatment (98%) and for maintenance pharmacotherapy (96%), but lower for supportive treatment (73.5%), use of an emergency plan (70.6%), psychotherapy (52.2%), group psychoeducation (47.2%), and mood monitoring (47%). Presence of a written treatment plan, a more specialized treatment setting, more years of education, and diagnosis of bipolar I disorder versus bipolar II, bipolar NOS, or schizoaffective disorder were significantly associated with better concordance.

Conclusion: In contrast to pharmacotherapy, psychosocial treatments are only implemented to a limited extend in everyday clinical practice in bipolar disorder. More effort is needed to implement non-pharmacological guideline recommendations for bipolar disorder.
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http://dx.doi.org/10.1186/s40345-018-0130-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195496PMC
October 2018

The circulating levels of CD4+ t helper cells are higher in bipolar disorder as compared to major depressive disorder.

J Neuroimmunol 2018 06 21;319:28-36. Epub 2018 Mar 21.

Erasmus MC, Department of Immunology, Rotterdam, The Netherlands.

Introduction: Clinical differentiation between bipolar disorder (BD) and major depressive disorder (MDD) is difficult. Research has therefore focused on discriminatory biological markers. Previous studies in MDD reported T cell deficits, while the limited studies in BD reported T cell activation. Studies directly comparing circulating numbers of T cells and T cell subsets between BD and MDD are lacking. The studies in the MOODINFLAME consortium make such a comparison possible.

Methods: The number of circulating leukocyte populations (lymphocytes, monocytes, NK cells, B cells, T cells, CD3+CD8+ T cytotoxic cells, CD3+CD4+ T helper cells, Th1, Th2, Th17 and T regulatory cells) was determined using FACS technology in a cohort of 83 euthymic BD patients, 8 BD patients with a current mood episode and 165 healthy controls (HC). Data were compared to those of 34 moderately and 56 severely depressed MDD patients.

Results: Compared to MDD patients, BD patients showed significantly increased levels of Th17, Th2, Th1 and T regulatory cells (all p < .02). In BD patients, levels of Th17 and T regulatory cells were increased compared to HC (p = .03, p = .02, respectively), while MDD patients showed decreased levels of Th17 and Th2 compared to HC (p = .03, p = .01, respectively). Of the various medications only SSRI/SNRI usage could explain part of the Th2 decrease in MDD.

Conclusion: This study shows CD4+ T helper cell deficits in MDD patients, while normal or even raised levels of these cells were found in BD patients. The differences in CD4+ T helper cell differentiation was most outspoken for Th17 cells.
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http://dx.doi.org/10.1016/j.jneuroim.2018.03.004DOI Listing
June 2018

Effectiveness of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment versus their combination in prevention of depressive relapse or recurrence (DRD study): a three-group, multicentre, randomised controlled trial.

Lancet Psychiatry 2018 05 3;5(5):401-410. Epub 2018 Apr 3.

Department of General Practice, University of Groningen, Groningen, Netherlands.

Background: Keeping individuals on antidepressants after remission or recovery of major depressive disorder is a common strategy to prevent relapse or recurrence. Preventive cognitive therapy (PCT) has been proposed as an alternative to maintenance antidepressant treatment, but whether its addition would allow tapering of antidepressants or enhance the efficacy of maintenance antidepressant treatment is unclear. We aimed to compare the effectiveness of antidepressants alone, with PCT while tapering off antidepressants, or PCT added to antidepressants in the prevention of relapse and recurrence.

Methods: In this single-blind, multicentre, parallel, three-group, randomised controlled trial, individuals recruited by general practitioners, pharmacists, secondary mental health care, or media were randomly assigned (10:10:8) to PCT and antidepressants, antidepressants alone, or PCT with tapering of antidepressants, using computer-generated randomised allocation stratified for number of previous depressive episodes and type of care. Eligible participants had previously experienced at least two depressive episodes and were in remission or recovery on antidepressants, which they had been receiving for at least the past 6 months. Exclusion criteria were current mania or hypomania, a history of bipolar disorder, any history of psychosis, current alcohol or drug abuse, an anxiety disorder that requires treatment, psychological treatment more than twice a month, and a diagnosis of organic brain damage. The primary outcome was time-related proportion of individuals with depressive relapse or recurrence in the intention-to-treat population, assessed four times in 24 months. Assessors were masked to treatment allocation, whereas physicians and participants could not be masked. This trial is registered with the Netherlands Trial Register, number NTR1907.

Findings: Between July 14, 2009, and April 30, 2015, 2486 participants were assessed for eligibility and 289 were randomly assigned to PCT and antidepressant (n=104), antidepressant alone (n=100), or PCT with tapering of antidepressant (n=85). The overall log-rank test was significant (p=0·014). Antidepressants alone were not superior to PCT while tapering off antidepressants in terms of the risk of relapse or recurrence (hazard ratio [HR] 0·86, 95% CI 0·56-1·32; p=0·502). Adding PCT to antidepressant treatment resulted in a 41% relative risk reduction compared with antidepressants alone (0·59, 0·38-0·94; p=0·026). There were two suicide attempts (one in the antidepressants alone group and one in the PCT with tapering of antidepressants group) and one death (in the PCT and antidepressants group) not related to the interventions during the 24 months' follow-up.

Interpretation: Maintenance antidepressant treatment is not superior to PCT after recovery, whereas adding PCT to antidepressant treatment after recovery is superior to antidepressants alone. PCT should be offered to recurrently depressed individuals on antidepressants and to individuals who wish to stop antidepressants after recovery.

Funding: The Netherlands Organisation for Health Research and Development.
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http://dx.doi.org/10.1016/S2215-0366(18)30100-7DOI Listing
May 2018

Effectiveness of maintenance therapy of lithium vs other mood stabilizers in monotherapy and in combinations: a systematic review of evidence from observational studies.

Bipolar Disord 2018 Feb 14. Epub 2018 Feb 14.

University Department of Psychiatry and Oxford Health NHS Foundation Trust, University of Oxford, Warneford Hospital, Oxford, UK.

Objectives: For the first time to present a systematic review of observational studies on the efficiency of lithium monotherapy in comparison with other maintenance mood stabilizers in monotherapy and in combination.

Methods: As part of the International Society for Bipolar Disorders (ISBD) Task Force on Lithium Treatment, we undertook a systematic literature search of non-randomized controlled observational studies on (i) lithium monotherapy vs treatment with another maintenance mood stabilizer in monotherapy and (ii) lithium in combination with other mood stabilizers vs monotherapy.

Results: In eight out of nine identified studies including a total of < 14 000 patients, maintenance lithium monotherapy was associated with improved outcome compared with another mood stabilizer in monotherapy, including valproate, lamotrigine, olanzapine, quetiapine, unspecified anticonvulsants, carbamazepine/lamotrigine, unspecified atypical antipsychotics and unspecified antipsychotics. Among the four identified studies including a total of > 4000 patients comparing maintenance combination therapy with maintenance monotherapy, a few combination therapies were found to be superior to monotherapy in some analyses, but many were not.

Conclusions: The results show the superiority in real life of lithium monotherapy compared with monotherapy with other maintenance mood stabilizers. The four largest register-based studies largely addressed confounding, but, as ever, residual confounding cannot be excluded. Nevertheless, the observational findings substantially add to the findings from randomized controlled trials, whose designs often limit the validity of comparison between medicines.
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http://dx.doi.org/10.1111/bdi.12623DOI Listing
February 2018

Lithium and Renal Impairment: A Review on a Still Hot Topic.

Pharmacopsychiatry 2018 Sep 18;51(5):200-205. Epub 2018 Jan 18.

Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark.

Introduction: Lithium is established as an effective treatment of mania, of depression in bipolar and unipolar disorder, and in maintenance treatment of these disorders. However, due to the necessity of monitoring and concerns about irreversible adverse effects, in particular renal impairment, after long-term use, lithium might be underutilized.

Methods: This study reviewed 6 large observational studies addressing the risk of impaired renal function associated with lithium treatment and methodological issues impacting interpretation of results.

Results: An increased risk of renal impairment associated with lithium treatment is suggested. This increased risk may, at least partly, be a result of surveillance bias. Additionally, the earliest studies pointed toward an increased risk of end-stage renal disease associated with lithium treatment, whereas the later and methodologically most sound studies do not.

Discussion: The improved renal outcome found in the more recent lithium studies may be a result of improved monitoring and focus on recommended serum levels (preferentially 0.6-0.8 mmol/L) as compared to poorer renal outcome in studies with patients treated in the 1960s to 1980s.
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http://dx.doi.org/10.1055/s-0043-125393DOI Listing
September 2018

The relationship between self-reported borderline personality features and prospective illness course in bipolar disorder.

Int J Bipolar Disord 2017 Sep 25;5(1):31. Epub 2017 Sep 25.

Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.

Background: Although bipolar disorder (BD) and borderline personality disorder (BPD) share clinical characteristics and frequently co-occur, their interrelationship is controversial. Especially, the differentiation of rapid cycling BD and BPD can be troublesome. This study investigates the relationship between borderline personality features (BPF) and prospective illness course in patients with BD, and explores the effects of current mood state on self-reported BPF profiles.

Methods: The study included 375 patients who participated in the former Stanley Foundation Bipolar Network. All patients met DSM-IV criteria for bipolar-I disorder (n = 294), bipolar-II disorder (n = 72) or bipolar disorder NOS (n = 9). BPF were assessed with the self-rated Personality Diagnostic Questionnaire. Illness course was based on 1-year clinician rated prospective daily mood ratings with the life chart methodology. Regression analyses were used to estimate the relationships among these variables.

Results: Although correlations were weak, results showed that having more BPF at baseline is associated with a higher episode frequency during subsequent 1-year follow-up. Of the nine BPF, affective instability, impulsivity, and self-mutilation/suicidality showed a relationship to full-duration as well as brief episode frequency. In contrast all other BPF were not related to episode frequency.

Conclusions: Having more BPF was associated with an unfavorable illness course of BD. Affective instability, impulsivity, and self-mutilation/suicidality are associated with both rapid cycling BD and BPD. Still, many core features of BPD show no relationship to rapid cycling BD and can help in the differential diagnosis.
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http://dx.doi.org/10.1186/s40345-017-0100-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610955PMC
September 2017

Seasonal affective disorder and non-seasonal affective disorders: results from the NESDA study.

BJPsych Open 2017 Jul 30;3(4):196-203. Epub 2017 Aug 30.

, PhD, Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Background: Seasonal affective disorder (SAD) is considered to be a subtype of depression.

Aims: To compare the clinical picture of SAD to non-seasonal affective disorders (non-SADs).

Method: Diagnoses according to the (DSM-IV) were established in 2185 participants of the Netherlands Study of Depression and Anxiety. The Seasonal Pattern Assessment Questionnaire was administered to diagnose SAD. Symptoms of depression and anxiety were measured with the Inventory of Depressive Symptoms, the Beck Anxiety Inventory and the Fear Questionnaire.

Results: Participants with SAD, participants with a lifetime bipolar disorder and participants with a lifetime comorbid anxiety and depressive disorder scored highest in terms of psychopathology in the past year. The seasonal distribution of major depressive episodes was not different for participants with or without SAD.

Conclusions: SAD may be a measure of severity of depression with a subjectively perceived worsening of symptoms in the winter months.

Declaration Of Interest: Y.M. has received research funding and served as a consultant for Royal Philips Electronics NV and The Litebook Company Ltd. W.A.N. has received grants from the Netherlands Organization for Health Research and Development, the European Union, the Stanley Medical Research Institute, Astra Zeneca, Eli Lilly, GlaxoSmithKline and Wyeth; has received honoraria/speaker's fees from Astra Zeneca, Pfizer, Servier and Wyeth; and has served in advisory boards for Astra Zeneca, Pfizer and Servier.

Copyright And Usage: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.
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http://dx.doi.org/10.1192/bjpo.bp.116.004960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572284PMC
July 2017
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